The
50th anniversary of the discovery of vitamin B12 came and went and nobody
noticed.There were no conferences
to mark the occasion, no fanfares, no speeches, not a mention in the press,
not even in the nutritional media."Vitamin
B12 isn't sexy," was the way a friend, a sports nutrition consultant,
put it."just
for old people, to keep them from getting anemic."Oh, yeah?Welcome
to the new story of vitamin B12.

There's
a buzz over B12 these days for two reasons, one scientific and the other
economic.First, the science:
Over the last decade or so, researchers have strongly implicated the toxic
amino acid homocysteine in a variety of disease states.Homocysteine
tends to accumulate in the body whenever B12 gets deficient, and this
accumulation has been linked with increased risk of Alzheimer's disease1,2,
cardiovascular disease3, chronic
fatigue syndrome/fibromyalgia4 and
multiple sclerosis5 among other conditions.

Folic
acid deficiency can also lead to increased homocysteine levels 
that's because folate and B12, in their active 'coenzyme' forms, are both
necessary cofactors for the enzymatic conversion of homocysteine to methionine.
Until recently it's been thought that the availability of folate was the
most important determinant of the body's ability to remethylate homocysteine.New
research has revealed that vitamin B12 is more important for homocysteine
disposal than previously believed5, 6,
7. In particular,
a study conducted among dialysis patients with kidney failure showed that
a monthly shot of B12 plus conventional oral folate was more effective
than high-dose folate without B12 in lowering elevated homocysteine6.

The
coenzyme form of vitamin B12 is known asmethylcobalamin
or methyl B12.It's the only form of vitamin B12 which can directly participate
in homocysteine metabolism.In
addition, converting homocysteine to methionine via methyl B12 generates
an increased supply of SAMe (S-adenosyl methionine), the body's most important
methyl donor.Indeed, some
of the benefits of methyl B12, such as protection from neurotoxicity,
appear to derive from increased production of SAMe8,
9.Methyl B12 has also
been reported to be neurotrophic or growth-promoting for nerve cells10,
11, a property which may help regenerate
central and peripheral nervous tissues damaged in disorders such as amyotrophic
lateral sclerosis12 and diabetic
peripheral neuropathy13.

All
of this scientific news is hot stuff, but it's still only half the story.The
other half is that starting around 1998, methylcobalamin first became
widely available in this country at an affordable price, thus offering
new options for treating B12 deficiencies and lowering elevated homocysteine.Before
then, methyl B12 had been enormously expensive and widely available only
in Japan, where it still remains a prescription medication.Today
any health-conscious American consumer can easily access the most powerful
known form of vitamin B12.

Methylcobalamin
and Cyanocobalamin

When
most of us think of vitamin B12, the molecule we really have in mind iscyanocobalamin or cyanoB12.As
its name suggests, cyano B12 has a cyanide group (CN) attached, whereas
methyl B12 carries a methyl group (CH3) instead.Very
little of the body's natural B12 is in the cyano form under normal circumstances;
exceptions are in cases of cyanide poisoning or chronic smoking, both
of which can raise cyanocobalamin levels. The fact that most of our vitamin
pills contain cyano rather than methyl B12 is largely an accident of history,
the result of using charcoal to filter extracts during the isolation of
B12.Unknown to the early
researchers who first isolated B12, the traces of cyanide present in such
charcoal rapidly convert all natural forms of B12, including methyl B12
into the more stable cyano form.As
a result, the discovery of the B12 coenzymes and their metabolic role
was delayed for years.

Whenever
we swallow a conventional vitamin pill, any cyano B12 present gets carried
along and absorbed by an intricate "bucket brigade" of B12-binding proteins.
Operating in the stomach and small intestine, this transport system provides
a very efficient mechanism for absorbing a few micrograms of B12, yet
is quickly swamped by anything larger.As
a result, only about 1% of a large oral dose of any form of B12
usually makes it into the bloodstream.Fortunately,
we can bypass intestinal absorption entirely by taking B12 sublingually.Sublingual
administration is a simple and effective way of substantially raising
blood levels by absorbing B12 through the oral mucosa.It's
also unquestionably the most convenient way to take B12, especially for
people taking supplements on a daily basis.

So
let's say we've taken a sublingual tablet and a significant amount of
B12 shows up in the bloodstream.End
of story?Not if it's cyano
B12.Most of the B12 naturally
circulating in the blood plasma is in the methyl form.Before
cyano B12 can join this metabolic pool and be properly utilized by the
body, it has to be stripped of its cyano group and 'reduced' (i.e., made
to gain electrons) in a time-consuming, multi-step process14.The
result of all this processing is a B12 molecule with its cobalt ion reduced
from the +3 to the +1 oxidation state, ready to take on a methyl group
and be distributed throughout the body as methyl B12.

It
should be obvious that there are certain advantages inherent in taking
methyl B12 as a supplement, versus 'ordinary' B12.For
one thing, methyl B12 doesn't have to engage the body's resources to convert
it into coenzyme form, it's already there.Even
more important is the fact that methylcobalamin is the most highly
reduced formof vitamin B12 possible; this makes methyl B12 a
very potent reducing agent (antioxidant) indeed.In
a body undergoing oxidative stress -- for example from a disease process
or from a diet deficient in antioxidants -- it's possible that methyl
B12 production can become impaired.A
similar derangement in the cellular synthesis of adenosyl B12 (another
reduced coenzyme form of B12 into which methyl B12 can be converted) is
already known to occur in association with vitamin E deficiency15.So
it makes sense to consume B12 in a form in which it's already metabolically
active and maximally reduced, and thereby put less of a strain
on our bodies' antioxidative capacity.

How
Much Is Enough?

How
much methyl B12 should be taken for optimal health?In
some studies on animals and humans, large doses (equivalent to 25-40 milligrams
per day for an adult human) were found to halt or improve neural degeneration10-12.The
problem is, nobody knows the long-term effects of such huge doses.A
more prudent approach would be to take about a tenth as much, say, 3 milligrams
per day (3,000 micrograms) as a maintenance dose, with the dose increased
as needed in cases of increased stress, oxidative or otherwise.

[A Note From Don
Bennett: The B12 I take and recommend, and the one that's mentioned
below, comes in 1,000 microgram tablets, and the bottle says "one
a day", but I don't take it everyday, just when I "feel"
like it, maybe every few days, and then it is usually 2,000 or 3,000
micrograms. See this
article I wrote on B12 for a resource for this B12 supplement. Also,
I would get a uMMA test done before beginning to take
supplementary B12 (it's a urine test). This will show if you need to
take any B12 or not (and this test is the gold standard for B12 utilization
and should not be confused with the B12 blood test that doctors usually
order). And if the test shows that you don't need to take any B12, you
shouldn't. But if this test shows that you are deficient (and most people
are), just how deficient you are will help determine the initial dose
to take, and this is the best reason for doing this test. This test
can be done at home and mailed to the lab. If you'd like a resource
for this test, see my B12
article.]

So
here's a belated 'Happy 50th Birthday' to B12.With
all of the health and pro-longevity benefits of methyl B12 now becoming
evident including warding off such age-related diseases as Alzheimer's1,
2, atherosclerosis3, rheumatoid
arthritis16 and possibly even cancer17,
18, it seems that the old vitamin's got some new life in it.May
it and we continue in partnership for many birthdays yet to come.

Two of the subjects' urinary Methyl Malonic
Acid (uMMA) normalized while the remaining subject's stayed slightly elevated
at 4.1 µg/mg creatinine (normal is < 4.0 µg/mg creatinine).
Thus, at a rate of 1-2 milligrams/day, methylcobalamin appears to be absorbed
at a high enough rate to improve B12 status in some vegans. Additionally,
this indicates that the methylcobalamin was able to improve the MMA pathway
which requires adenosylcobalamin (in other words, methylcobalamin was
apparently converted into adenosylcobalamin in these people).